The development of assays for product safety testing based on human pluripotent stem cell lines requires careful evaluation of the starting cell line and qualification of the protocol to deliver the final cells for testing. In the is presentation will consider experiences in addressing these issues in the Seurat-1 EC/Colipa funded programme and new initiatives in the development of best practice for stem cell culture and assay development.

- Using relevant cells for high content analysis - HipSci: diverse constituents in genomics, proteomics, cell biology and clinical genetics for a national iPS cell resource to carry out cellular genetic studies. - The Stem Cell Hotel: building a dedicated space for collaborative phenotyping within the premises of the Centre for Stem Cells & Regenerative Medicine at KCL.

An overview of the applications of two validated technologies CombiCult® and ProScreen™ on the discovery of small molecule regenerative drugs for osteoarthritis, multiple sclerosis and muscular dystrophy - an open innovation partnership with GSK, will be presented.

Human cell types differentiated from induced pluripotent stem cells (iPSCs) offer an attractive source of cellular material for both toxicity screening and drug discovery because of the biologically relevant systems they can represent in vitro. The iPSC technology is a key element for modeling human biology in a dish, which is otherwise difficult to explore using conventional cell lines, primary cells, or animal models. Our approach is to generate iPSC-derived cell types with high quality, purity, and unlimited quantities, design relevant assays with cells derived from apparently healthy donors, and develop disease models using environmental stimuli or disease-specific, patient-derived cells. Current efforts are aimed at generating large iPSC clone banks from diverse diseased backgrounds that will serve to dramatically expand access to cell models offering new tools and opportunities for phenotypic drug discovery.

In my talk I will present the large-scale generation of neuronal progenitors derived from Fragile X patients and their use to develop a high-content imaging assay to run a HTS to identify compounds counteracting the epigenetic gene silencing in Fragile X syndrome.

Generation of spinal cord neurons and muscles from pluripotent stem cells with precise positional identity is crucial for neuromuscular disease modeling. I will focus on the in vitro generation of a neuromesodermal (NMP) progenitor population from pluripotent stem cells, an advancement that gives unprecedented access to the development of new models to study neuromuscular diseases.

The talk will give a brief overview of the area, outline how my group became involved in the field and cover contributions we have made, including the expansion of pluripotent and multipotent stem cells and how we are aiming to translate our work to the clinic for regenerative therapies. As a representative example the discovery process for new small molecule modulators to induce the differentiation of neural stem cells both in vitro and directly in vivo following systemic administration will be described.

I will discuss how lineage decisions of human stem cells model gastrulation and thereby achieve growth factor-induced differentiation to specific cell types; how transcription factor-based forward programming provides an alternative strategy for differentiation of clinically relevant cells; and how interspecies post-implantation chimeras can be used to functionally validate human pluripotent stem cells for use in regenerative medicine.

Tuesday, 7 March 2017

We have developed three-dimensional culture systems for cerebellum and cerebral cortex using human pluripotent stem cells. We are investigating the pathogenesis of the intractable neurological diseases using in vitro disease models utilizing the patient-derived iPS cells.

Metabolic disorders represent a global health challenge and the development of new therapeutics are urgently needed. Here, I will describe how human pluripotent stem cells can be exploited to develop new platforms for drug screening and disease modelling.

AstraZeneca applies advanced technologies for generation and validation of iPS cell derived models for drug discovery. Data from two cellular-platforms are presented, where we have used these tools to monitor cell-model development and compare to existing primary cell models.

In my talk I will introduce polymer microarray technology and describe how this approach has been used in a large number of stem cell based applications, notably polymer discovery able to support highly functional hESC-derived hepatocyte like cells and the discovery of a substrate, able to enrich CSC's.

I will present the latest results from our work on the Human Induced Pluripotent Stem Cell Initative (www.hipsci.org), which aims to generate large numbers of IPSCs from healthy individuals and disease volunteers. I will also discuss some of our work using HIPSCI lines to study a range of cell lineage.

Human stem cell-derived cardiomyocytes (hiPS-CMs) are increasingly used for screening of cardiac safety liabilities within the pharmaceutical industry. Optimization of the Ca2+ transient assay together with in-depth characterization of hiPS-CMs is essential to evaluate and improve cardiac risk assessment within drug development.